The objective of the research is to develop new research projects on cellular and molecular changes that occur during aging. Dr. Hoffee will analyze the properties of deoxyribose-5-aldolase in rat liver. The enzyme may play a key role in the regulation of the cell cycle, and exhibits different properties in old animals. The mechanisms involved in the changes will be analyzed by studying the purified protein. Drs. Lombardi and Ove will study carcinogenesis. The induction of hepatic tumors by chemical carcinogens will be studied as a function of age in control animals and in animals subjected to nutritional deprivation. The promotional phase of neoplasia will be studied in similar animals, and also, by studying the growth of transplantable hepatomas. As a first step to elucidate possible mechanisms, the activity of DNA repair enzymes will be studied. The research should lead to an understanding of age-related changes in connective tissues, enzyme activity, and tumor development. Finally, Dr. Tong will study the mechanisms involved in the decrease in myocardial contractility as a function of age. The first approach will be to analyze the role of the adenylate cyclase system.